Category Archives: Drugs for Diabetes

From 2012: Largest Healthcare Fraud Settlement In History Involves T2 Diabetes Drug Avandia

Your friendly neighborhood drug supplier

Your friendly neighborhood drug supplier

This will help you understand why I favor diet modification over drug therapy for type 2 diabetes:

“Global health care giant GlaxoSmithKline LLC (GSK) agreed to plead guilty and to pay $3 billion to resolve its criminal and civil liability arising from the company’s unlawful promotion of certain prescription drugs, its failure to report certain safety data, and its civil liability for alleged false price reporting practices, the Justice Department announced today. The resolution is the largest health care fraud settlement in U.S. history and the largest payment ever by a drug company. GSK agreed to plead guilty to a three-count criminal information, including two counts of introducing misbranded drugs, Paxil and Wellbutrin, into interstate commerce and one count of failing to report safety data about the drug Avandia to the Food and Drug Administration (FDA). Under the terms of the plea agreement, GSK will pay a total of $1 billion, including a criminal fine of $956,814,400 and forfeiture in the amount of $43,185,600. The criminal plea agreement also includes certain non-monetary compliance commitments and certifications by GSK’s U.S. president and board of directors. GSK’s guilty plea and sentence is not final until accepted by the U.S. District Court. GSK will also pay $2 billion to resolve its civil liabilities with the federal government under the False Claims Act, as well as the states. The civil settlement resolves claims relating to Paxil, Wellbutrin and Avandia, as well as additional drugs, and also resolves pricing fraud allegations.”

Source: GlaxoSmithKline to Plead Guilty and Pay $3 Billion to Resolve Fraud Allegations and Failure to Report Safety Data | OPA | Department of Justice

Regarding Avandia:

“The United States alleges that, between 2001 and 2007, GSK failed to include certain safety data about Avandia, a diabetes drug, in reports to the FDA that are meant to allow the FDA to determine if a drug continues to be safe for its approved indications and to spot drug safety trends. The missing information included data regarding certain post-marketing studies, as well as data regarding two studies undertaken in response to European regulators’ concerns about the cardiovascular safety of Avandia. Since 2007, the FDA has added two black box warnings to the Avandia label to alert physicians about the potential increased risk of (1) congestive heart failure, and (2) myocardial infarction (heart attack). GSK has agreed to plead guilty to failing to report data to the FDA and has agreed to pay a criminal fine in the amount of $242,612,800 for its unlawful conduct concerning Avandia.”

And…

“In its civil settlement agreement, the United States alleges that GSK promoted Avandia to physicians and other health care providers with false and misleading representations about Avandia’s safety profile, causing false claims to be submitted to federal health care programs. Specifically, the United States alleges that GSK stated that Avandia had a positive cholesterol profile despite having no well-controlled studies to support that message. The United States also alleges that the company sponsored programs suggesting cardiovascular benefits from Avandia therapy despite warnings on the FDA-approved label regarding cardiovascular risks. GSK has agreed to pay $657 million relating to false claims arising from misrepresentations about Avandia. The federal share of this settlement is $508 million and the state share is $149 million.”

 

Are Some T2 Diabetes Drugs Better Than Others?

From MPT:

“The number of type 2 diabetes drugs that have a proven cardiovascular benefit jumped from one to three this year, highlighting the changing landscape for diabetes treatments.”

Source: Year in Review: Type 2 Diabetes | Medpage Today

The article notes that liraglutide (Victoza), a GLP-1 analogue, was associated with a 13% relative risk reduction in a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

Semaglutide, an experimental GLP-1 analogue, also has evidence for cardiovascular death prevention.

Another diabetes drug, Jardiance or empagliflozin, also has evidence for cardiovascular death prevention. Jardiance is an SGLT2 inhibitor.

Read the full MPT article for more details. I find the cost of these drugs to be an interesting yet little discussed detail.

Let’s assume these drugs actually reduce cardiovascular disease risk in T2 diabetics. What if they increase death and disease rates from cancer and infection? You don’t hear much about that, do you?

We still don’t know much about the long-term adverse effects of most of our diabetes drugs. That’s one reason I tend to favor diet modification as a primary diabetes treatment.

No degludec up in here!

FDA Says Jardiance Can Be Marketed as Cardiovascular Death-Defying

Jardiance is a diabetes drug in the class called SGLT2 inhibitors.

How do they work? Our kidneys filter glucose (sugar) out of our bloodstream, then reabsorb that glucose back into the bloodstream. SGLT2 inhibitors impair that reabsorption process, allowing some glucose to be excreted in our urine. You could call it a diuretic effect. For example, an SGLT 2 inhibitor called dapagliflozin, at a dose of 10 mg/day, causes the urinary loss of 70 grams of glucose daily.

How drugs like this could prevent cardiovascular disease in type 2 diabetics is a mystery to me.

From MPT:

“The diabetes drug empagliflozin (Jardiance) may be marketed for prevention of cardiovascular death in patients with type 2 diabetes and co-existing cardiovascular disease, the FDA said Friday.

It’s the first such claim ever allowed for a diabetes drug.

Empagliflozin, first approved in 2014, is an inhibitor of the sodium-glucose co-transporter 2 (SGLT2) pathway, reducing blood glucose by causing it to be excreted in urine.Its benefit for cardiovascular risk reduction was demonstrated in the so-called EMPA-REG trial, results of which were reported in 2015.”

Source: Jardiance Wins CV Prevention Indication | Medpage Today

Insulin cost in U.S. doubled between 2002-2013

This is NOT an insulin rig!

This is NOT an insulin rig!

You can’t blame inflation for the cost increase. I’m not sure the link below explains why.

Just this morning I was listening to AM “talk radio” and someone said her husband’s two insulins cost $1,400/month (USD). That’s ridiculous. He was between jobs and had lost his health insurance that had been paying for insulin.

If you’re worried about the cost of insulin, you can take action today to reduce your required dose: lose the excess weight, eat fewer carbohydrates, improve your insulin sensitivity with exercise.

From Reuters:

“The cost of the hormone insulin, one of the most important treatments for diabetes, rose nearly 200 percent between 2002 and 2013, according to a new study.

While other diabetes medications also increased in price, total spending on insulin in 2013 was greater than the combined spending on all those other drugs, researchers report in JAMA.

“The large increase in costs can largely be explained (by) much greater use of newer types of insulin known as analog insulins,” said senior author Philip Clarke, of the University of Melbourne in Australia. “While these drugs can be better for some patients, they are much more costly than the human insulin they replaced.”

Source: Insulin cost in U.S. more than doubles between 2002-2013 | Reuters

Steve Parker, M.D.

Study Finds No Survival Advantage for Eight Classes of Type 2 Diabetes Drugs

 

A waste of money?

A waste of money?

A multinational group of researchers tried to determine which drugs for type 2 diabetes were better at prolonging life and preventing cardiovascular deaths. They reviewed the existing literature (i.e., they did a meta-analysis of prior clinical studies.

There are no clear winners. Placebo worked as well as the eight drug classes examined!

Unfortunately, the abstract doesn’t say how long the clinical studies lasted, only mentioning that they were at least 24 weeks long. It’s quite possible it would take at least three to five years to see an effect on death rates.

Selected quotes:

“Eight different diabetes drug classes examined in a meta-analysis failed to demonstrate improved cardiovascular or all-cause mortality compared with placebo.Researchers analyzed 301 randomized clinical trials of patients with type 2 diabetes, and found that, metformin outperformed some other drug classes for its effect on hemoglobin A1c levels, there were no significant differences in mortality — including when placebo was included as a drug class.”

***

“A central finding in this meta-analysis was that despite more than 300 available clinical trials involving nearly 120,000 adults and 1.4 million patient-months of treatment, there was limited evidence that any glucose-lowering drug stratified by coexisting treatment prolonged life expectancy or prevented cardiovascular disease,” the authors wrote.”

***

“The authors wrote that their findings are consistent with guidelines from the American Diabetes Association, which — like the algorithm from the American Association of Clinical Endocrinologists — recommend that metformin monotherapy be used for the initial treatment of patients with type 2 diabetes. “Based on this review, clinicians and patients may prefer to avoid sulfonylureas or basal insulin for patients who wish to minimize hypoglycemia, choose GLP-1 receptor agonists when weight management is a priority, or consider SGLT-2 inhibitors based on their favorable combined safety and efficacy profile,” the authors wrote.”

Source: No Clear Survival Benefit Seen Among Diabetes Drugs | Medpage Today

Optimal Insulin Injection Guidelines from FITTER

Going in at a 45 degree angle with a 6 mm needle

Going in at a 45 degree angle with a 6 mm needle

“Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015.”

Source: New Insulin Delivery Recommendations – Mayo Clinic Proceedings

Here are some bullet points that most insulin users need to know:

  • Average skin thickness is 2 to 2.5 mm, with 90% of people under 3.25 mm.
  • Use the shortest needles: 6 mm for syringes, 4 mm for pen injectors. The short needles help you avoid injections into muscle. Injection into muscle increases risk of hypoglycemia and wide blood glucose excursions.
  • Acceptable injection sites: abdomen, thighs, buttocks, upper arms (usually on the back of the arm).
  • If an arm site is chosen with a 6 mm needle, inject into a lifted skin fold (otherwise you might hit muscle).
  • When using the 6 mm needle, inject into a lifted skinfold if you are a child or normal-weight adult. Alternatively, insert the needle at a 45 degree angle.
  • The preferred site for regular insulin (soluble human insulin) is the abdomen, for faster absorption.
  • Use needles only once. (Admittedly, many get away with multiple uses without much trouble.)
  • Don’t inject into lipohypertrophy areas. Lipohypertrophy eventually is an issue in half of insulin users. It is a localized area of swelling or lumpiness at the site of prior injections. It’s often easier to feel than to see. Injection into these areas causes erratic absorption of insulin, with potential widely fluctuating and unpredictable blood sugar levels.
  • Rotate injection sites to avoid lipohypertrophy.
  • If using cloudy insulins (e.g., NPH and some pre-mixed insulins), gently roll and tip the vial or pen until the solution is milk white.

Click here to read about…

  • How to roll and tip a vial to make cloudy insulin milk white.
  • Proper needle disposal.
  • Insulin infusion sets for continuous subcutaneous insulin injection via pumps.

Steve Parker, M.D.

Are These Two Diabetes Drugs Better Than the Others?

Better living through chemistry

Empagliflozin is a pill. Liraglutide is a once-daily subcutaneous injection.

The two drugs in question are empagliflozin (aka Jardiance) and liraglutide (aka Victoza). Both are used to treat type 2 diabetes, not type 1.

A major problem we have with most diabetes drugs is that while they do lower blood sugars, we don’t have much evidence on whether they actually prolong life and prevent bad outcomes like heart attacks, strokes, cancer, blindness, kidney failure, amputations, and serious infections.

It gets even more complicated. For instance, a given drug may eventually be proven to prolong life by a year via prevention of death from heart disease, while at the same time increasing the risk of spending that last year bedridden from a stroke.

It’s extremely difficult and costly to suss out these issues. It requires large clinical trials wherein half of the PWDs (people with diabetes) are treated with a particular drug, and the other half are treated with “standard therapy.” Five or 10 years later you compare clinical endpoints between the two groups. A couple studies have done this recently.

A blogger I follow, Larry Husten, wrote the following:

But it was the secondary goal of these trials that led to the transformation of the field. Baked into the trial design was the provision that if they were able to establish noninferiority then the trial investigators were permitted to test for superiority. The second phase began when Empa-Reg became the first trial to convincingly show a clear benefit, including a reduction in cardiovascular death and a reduction in hospitalization for heart failure. with empagliflozin (Jardiance, Merck). Then, more recently, the LEADER trial showed a significant reduction in cardiovascular events with liraglutide (Victoza, Novo Nordisk). In both trials nearly all the patients had significant established cardiovascular disease—precisely the population that cardiologists are likely to see.

Click the embedded links above for more details. Even better, read the original research reports if you have the time and knowledge. I support my family with a full-time job taking care of patients, so it will be a while (if ever) before I can dig into this further. (When my book sales make me independently wealthy, I’ll have more time for this!)

diabetic diet, low-carb Mediterranean Diet, low-carb, Conquer Diabetes and Prediabetes

Analyzing clinical reports requires a good grasp of logic, statistics, and basic science

Are the LEADER and Empa-Reg trials valid? Yeah, maybe. In an ideal world, other investigators would try to replicate the results with additional clinical trials. Are the published results free of fraud and bias? I don’t know.

Because we don’t know the long-term effects of many of our diabetes drugs, I favor doing as much as possible to control blood sugars with diet, exercise, and weight management.

Stay tuned for future developments.

Steve Parker, M.D.

PS: Just because one drug in a class of drugs reduces bad clinical outcomes, it doesn’t mean all drugs in the class do.

PPS: If it’s hard for you to pronounce empagliflozin and liraglutide, some of my books don’t even have them.

Drugs for Diabetes: Insulin Degludec (Tresiba) – A New Long-Acting Insulin

Tresiba joins other long-acting insulins like insulin glargine (Lantus), insulin detemir (Levemir), and good ol’ NPH insulin. While FDA-approved in the U.S. only this year, it’s been used in other countries for some time. Insulin degludec will have different names depending on the country.

Who Is It For?

  • Adults with type 1 and 2 diabetes
  • Not for diabetic ketoacidosis
  • We have no good data on use in children (under 18), pregnant women, and nursing mothers

How Long Does It Work?

It will last for at least 30 hours in most users. After that, effectiveness starts to taper off but some effect may be seen as long as 42 hours after the injection.

What Is Its Role In Treating Diabetes?

Insulin degludec is a basal insulin, meaning that it runs in the background continuously. It’s not designed to reduce blood sugar that rises after a meal. If your pancreas still makes insulin, release of that insulin may reduce after-meal glucose levels adequately. Otherwise, after-meal glucose elevations are addressed with bolus insulin injections. Bolus-type insulins are the rapid-acting ones like Humalog and Novolog.

Most NPH insulin users, and some insulin glargine (Lantus) users, need the injection twice daily. Because of its long duration of action, Triseba users should never need more than one injection daily. I don’t have much experience with Levemir because the hospital where I work doesn’t stock it.

Triseba users should take it at about the same time daily. If you miss that time by up to five or six hours either way, it probably won’t matter.

What’s the Dose?

For type 2 diabetics who have never used insulin, the starting dose is typically 10 units/day.

For type 1’s switching from other insulins, the usual starting dose is one-third to one-half of the total daily insulin dose, plus rapid-acting bolus insulin around meal times for the remainder.

Change the dose no more often than every three or four days.

How Much Does It Cost?

I don’t know. Likely more than some of the other basal insulins.

Steve Parker, M.D.

PS: Click here for full prescribing information.

PPS: If glargine, degludec, and detemir sound like Greek to you, you’ll appreciate my book.

No degludec up in here!

No degludec up in here!

More Patients With Impaired Kidney Function Qualify for Metformin

Recently the U.S. Food and Drug Administration revised their guidelines for physicians regarding use of metformin in patients with kidney impairment. This may make more patients candidates for the drug.

Physicians have been advised for years that type 2 diabetics with more than minimal kidney impairment should not be given metformin. Why? Metformin in the setting of kidney failure raises the risk of lactic acidosis.

The traditional test for kidney impairment is a blood test called creatinine. When kidneys start to fail, serum creatinine rises. Another way to measure kidney function is eGFR, which takes into account creatinine plus other factors.

By the way, you can’t tell about your kidney function simply from the way you feel; by the time you have signs or symptoms of renal failure, the process is fairly advanced.

The FDA now recommends not using  metformin if your eGFR (estimated glomerular function rate) is under 30 ml/min/1.73 m squared), and use only with extreme caution if eGFR drops below 45 while using metformin. Don’t start metformin if eGFR is between 30 and 45. Your doctor can calculate your eGFR and should do so annually if you take metformin.

Steve Parker, M.D.

Do SGLT2 Inhibitors Increase the Risk of Amputations in Diabetics?

Good question. But we don’t know the answer yet.

European authorities and even the U.S. Food and Drug Administration are looking into the possible connection. Stay tuned. Visit The Low Carb Diabetic site (link below) for more details.

“The European Medicines Agency (EMA)’s Pharmacovigilance Risk Assessment Committee (PRAC) has extended the scope of its investigation into the possible link between the sodium glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (Invokana, Vokanamet, Janssen) and amputations to include other drugs of the same class.

Now, the PRAC’s review will include the other SGLT2 inhibitor medicines dapagliflozin (Farxiga, Xigduo XR, AstraZeneca), and empagliflozin (Jardiance, Boehringer Ingelheim), based on the determination that the potential risk may be relevant for them as well.”

Source: The Low Carb Diabetic: EMA Extends Amputation Investigation to All SGLT2 Inhibitors

Steve Parker, M.D.

PS: SGLT2 inhibitors are the drugs that reduce blood glucose by shunting it into your urine. Makes more sense to me instead to reduce your blood sugar by eating fewer carbohydrates, the primary source of blood sugar in most folks.

Update May 17, 2017: On May 16, 2017, the U.S. Food and Drug Administration ruled that canagliflozin doubles the risk of foot and leg amputations, compared to placebo.